Tourette Syndrome (TS) is an autosomal dominant neuropsychiatric disorder affecting up to one person in 2,500 and is characterized by a range of neurological and behavioral symptoms. Such symptoms include: (A) the presence of both motor and vocal tics at some time during the illness, although not necessarily concurrently; (B) the occurrence of quasi-daily tics throughout a period of time exceeding one year; (C) variance in the clinical phenomenology of the tics; and (D) marked distress or significant impairment in social, occupational, or other important areas of functioning. Patients with TS also often suffer from co-morbid disorders such as Obsessive-Compulsive Disorder (OCD), Attention-Deficit Hyperactivity Disorder (ADHD), anxiety disorders, mood disorders, and panic disorders.
Tics experienced by a sufferer of TS can be transient or acute, and simple or complex. Motor tics generally include eye blinking, nose twitching, grimacing, muscle tensing, hopping, touching objects or others, and rapid jerking of any part of the body. Vocal or phonic tics typically include coughing, spitting, grunting, barking, hissing, sucking sounds, gurgling, screeching, whistling, palilalia, echolalia, and coprolalia.
The etiology and pathophysiology of TS are currently unknown. However, pharmacological and metabolic evidence suggests the involvement of several neurochemical systems, such as the dopaminergic, noradrenergic, GABAergic, and serotonergic mechanisms for example, and implicates neurotransmission dysfunction with the disorder.
Historically, attempts at treating TS by psychotherapeutic and behavior modification approaches were not encouraging in terms of dramatic, lasting improvement. Thus, the pursuit of behavioral strategies for decreasing the occurrence of tics has diminished. Current treatment of TS includes the administration of medications which are prescribed for neurotransmitter disorders. For example, neuroleptic drugs (i.e. those which reduce the amount of dopamine in the CNS) such as haloperidol, pimozide, fluphenazine, and chloropromazine have been administered to TS patients with success, but with side effects such as tardive dyskinesia, akinesia, increased appetite and weight gain, amenorrhea, Q and T wave changes, hypotension, and impotence. Other drugs such as clonidine (an antihypertensive), clonazepam (an anticonvulsant), and various antidepressants have been used to treat TS symptoms, but also induce side effects in the patient such as, for example, impotence.
Moreover, compounds that modulate activity of various receptors have been suggested as treatment due to a decreased number of receptors in the brains of patients suffering CNS disorders. (Cosford et al., U.S. Pat. No. 5,868,473 and Kerrigan et al., U.S. Pat. No. 5,767,116). Additionally, nicotine pharmacology has been suggested in suppressing TS. (Bencherif et al., U.S. Pat. No. 5,731,314). It has also been suggested that TS is caused by the supply of tryptophan to the brain, and TS symptoms have been treated by regulating the supply of tryptophan to the brain. (Richardson et al., U.S. Pat. No. 5,670,539).
Stimulants such as methylphenidate, dextroamphetamine, and pemoline may be prescribed for hyperactivity and ADHD, but often lead to an increase in the tics in TS. Antidepressants such as fluoxetine and clomiprimine are often prescribed to treat OCD symptoms. However, such antidepressants may also induce side effects such as muscle weakness, seizures, constipation, and impotence.
Although other pharmacological methods of treatment of TS are available, such methods have not proven to be highly satisfactory and can be accompanied by severe side-effects. What is needed is an improved method for the treatment of CNS disorders, including but not limited to Tourette Syndrome, without the induction of side effects in the patient such as, for example, impotence.